Multiple myeloma(MM)is the second most common hematological tumor characterized by the proliferation of monoclonal plasma cells.Melphalan(MEL)is commonly used in the treatment of MM and is especially essential for pat...Multiple myeloma(MM)is the second most common hematological tumor characterized by the proliferation of monoclonal plasma cells.Melphalan(MEL)is commonly used in the treatment of MM and is especially essential for patients undergoing autologous stem cell transplantation(ASCT).Although many drugs for MM have been developed in recent years,chemotherapy followed by ASCT remains the optimal option.Melphalan,the backbone of the conditioning regimen,brings severe toxicities at a high dose.Nanodrug delivery systems enable drugs to be highly effective and have low toxicity.In this study,methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer(MPEG-PDLLA)was chosen to encapsulate melphalan,and the characteristics,effectiveness,and safety of MEL/MPEG-PDLLA in vitro and in vivo were investigated.MEL/MPEG-PDLLA showed slow release and was easily engulfed by MM cells despite a result of the antitumor assay comparable to that of free melphalan in vitro.The in vivo results showed that MEL/MPEG-PDLLA could significantly alleviate tumor burden and prolong survival time without increasing the toxicity to vital organs.In addition,MEL/MPEG-PDLLA could significantly reduce the damage to the intestinal mucosa caused by melphalan.In conclusion,MEL/MPEG-PDLLA shows improved antitumor activity and has the potential to alleviate pains of MM patients undergoing ASCT.展开更多
Colorectal cancer(CRC)is a common digestive tract tumor worldwide.Specific microorganisms,including Fusobacterium nucleatum(F.nucleatum)and Escherichia coli(E.coli),are abundant in colonic mucosa and can promote the c...Colorectal cancer(CRC)is a common digestive tract tumor worldwide.Specific microorganisms,including Fusobacterium nucleatum(F.nucleatum)and Escherichia coli(E.coli),are abundant in colonic mucosa and can promote the cancer progression and malignancy.Therefore,a therapeutic strategy is proposed to deliver effective drugs to colorectum for both anticancer and antibacteria.Here we used thin-film dispersionmethod to encapsulate hemiprotonic phenanthroline-phenanthroline^(+)(ph-ph^(+))into nanomicelle.The results showed that the drug-loading nanomicelle had good dispersion,and the particle size was about 28 nm.In vitro assay indicated that the nanomicelle was active against CRC-related obligate and facultative anaerobes.In human CRC cells,the nanomicelle could effectively inhibit cell proliferation and induce apoptosis.In vivo distribution showed that the nanomicelle could release ph-ph^(+) mainly in the colorectum.In CRC model mice,the nanomicelle significantly reduced tumor number and volume,and decreased the bacteria load and colorectal inflammation.Together,the study identifies that the ph-ph^(+) nanomicelle has the potential to apply in treating CRC,and also suggests that anticancer combined with antimicrobial therapy would be a feasible way for CRC therapy.展开更多
Nanomedicine with high specificity has been a promising tool for cancer diagnosis and therapy.However,the successful application of nanoparticle-based superficial cancer therapy is severely hindered by restricted deep...Nanomedicine with high specificity has been a promising tool for cancer diagnosis and therapy.However,the successful application of nanoparticle-based superficial cancer therapy is severely hindered by restricted deep tumor tissue accumulation and penetration.Herein,a self-assembly nanomicelle dissolving microneedle(DMN)patch according to the“nano in micro”strategy was conducted to co-deliver a first-line chemotherapeutic agent paclitaxel(PTX),and a photosensitizer IR780(PTX/IR780-NMs@DMNs)for chemo-photothermal synergetic melanoma therapy.Upon direct insertion into the tumor site,DMNs created a regular and multipoint three-dimensional drug depot to maximize the tumor accumulation.Accompanied by the DMN dissolution,the composition of the needle matrixes self-assembled into nanomicelles,which could efficiently penetrate deep tumor tissue.Upon laser irradiation,the nanomicelles could not only ablate tumor cells directly by photothermal conversion but also trigger PTX release to induce tumor cell apoptosis.In vivo results showed that compared with intravenous injection,IR780 delivered by PTX/IR780-NMs@DMNs was almost completely accumulated at the tumor site.The antitumor results revealed that the PTX/IR780-NMs@DMNs could effectively eliminate tumors with an 88%curable rate without any damage to normal tissues.This work provides a versatile and generalizable framework for designing self-assembly DMN-mediated combination therapy to fight against superficial cancer.展开更多
[Objectives]To prepare plumbagin nanomicelle(PLB-N)in-situ gel,and optimize the formulation and process.[Methods]PLB-N was prepared by self-assembly method,and the optimal formulation of PLB-N in-situ gel was determin...[Objectives]To prepare plumbagin nanomicelle(PLB-N)in-situ gel,and optimize the formulation and process.[Methods]PLB-N was prepared by self-assembly method,and the optimal formulation of PLB-N in-situ gel was determined by orthogonal experiment design and single factor method.[Results]The optimal preparation process for PLB-N was a drug to lipid ratio of 1:3,a Tween 80 content of 5%,an ethanol content of 7.5%of the hydration medium,a magnetic stirring speed of 2200 rpm,a stirring time of 30 min,and an ultrasound time of 10 min.The optimal formulation of PLB-N in-situ gel was 22%of poloxamer 407,6%of poloxamer 188,and 1:1 of PLB-N to water.The encapsulation efficiency of PLB-N prepared with the optimal formula was(95.8%±0.4%),and the average particle size was(75.19±1.14)nm,and the Zeta potential was(-20.73±1.19)mv.[Conclusions]PLB-N in-situ gel had stable and reliable preparation process,uniform content,and broad application prospects.展开更多
Amphiphilic CS-SA polymers were prepared using the SA modified by small molecule water-soluble chitosan, and CS-SA nanomicelles and FF/CS-SA nanomicelles were prepared by using CSSA polymers as the material with dialy...Amphiphilic CS-SA polymers were prepared using the SA modified by small molecule water-soluble chitosan, and CS-SA nanomicelles and FF/CS-SA nanomicelles were prepared by using CSSA polymers as the material with dialysis-ultrasound method. CS-SA polymers, CS-SA nanomicelles, and FF/CS-SA nanomicelles were characterized by FT-IR, TGA, and SEM. Results showed that the SA was grafted to the amino of CS by amide bond. CS-SA nanomicelles and FF/CS-SA nanomicelles were spherical, smooth without fold. The influence of different molar ratio of FF to CS-SA polymers on the encapsulation efficiency and drug-loading rate determined the best molar ratio that was 1：1.09. In vitro release experiments, drug release performance study found that hydrophobic drug releasing from FF/CS-SA nanomicelles presented sustainedrelease. In vitro bacteriostasis experiments, when the concentration was higher than 4.98 mg/mL, FF/CSSA nanomicelles had antibacterial action and a positive correlation with concentration. The results revealed that amphiphilic chitosan derivative nanomicelles were carriers with broad prospects, increasing solubility of hydrophobic drugs and presenting sustained release for hydrophobic drugs, which provided a new research idea for drug delivery and targeted drug delivery of hydrohobic drugs.展开更多
All-in-one treatments represent a paradigm shift in future medicine.For example,inflammatory bowel disease(IBD)is mainly diagnosed by endoscopy,which could be applied for not only on-site monitoring but also the intes...All-in-one treatments represent a paradigm shift in future medicine.For example,inflammatory bowel disease(IBD)is mainly diagnosed by endoscopy,which could be applied for not only on-site monitoring but also the intestinal lesion-targeted spray of injectable hydrogels.Furthermore,molecular conjugation to the hydrogels would program both lesion-specific adhesion and drug-free therapy.This study validated this concept of all-in-one treatment by first utilizing a well-known injectable hydrogel that underwent efficient solution-to-gel transition and nanomicelle formation as a translatable component.These properties enabled spraying of the hydrogel onto the intestinal walls during endoscopy.Next,peptide conjugation to the hydrogel guided endoscopic monitoring of IBD progress upon adhesive gelation with subsequent moisturization of inflammatory lesions,specifically by nanomicelles.The peptide was designed to mimic the major component that mediates intestinal interaction with Bacillus subtilis flagellin during IBD initiation.Hence,the peptide-guided efficient adhesion of the hydrogel nanomicelles onto Toll-like receptor 5(TLR5)as the main target of flagellin binding and Notch-1.The peptide binding potently suppressed inflammatory signaling without drug loading,where TLR5 and Notch-1 operated collaboratively through downstream actions of tumor necrosis factor-alpha.The results were produced using a human colorectal cell line,clinical IBD patient cells,gut-on-a-chip,a mouse IBD model,and pig experiments to validate the translational utility.展开更多
基金supported by the National Natural Science Foundation of China(Nos.U21A20417,31930067,32271450,31700868)PostDoc Research Project,West China Hospital,Sichuan University(No.2020HXBH165)1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYGD18002)。
文摘Multiple myeloma(MM)is the second most common hematological tumor characterized by the proliferation of monoclonal plasma cells.Melphalan(MEL)is commonly used in the treatment of MM and is especially essential for patients undergoing autologous stem cell transplantation(ASCT).Although many drugs for MM have been developed in recent years,chemotherapy followed by ASCT remains the optimal option.Melphalan,the backbone of the conditioning regimen,brings severe toxicities at a high dose.Nanodrug delivery systems enable drugs to be highly effective and have low toxicity.In this study,methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer(MPEG-PDLLA)was chosen to encapsulate melphalan,and the characteristics,effectiveness,and safety of MEL/MPEG-PDLLA in vitro and in vivo were investigated.MEL/MPEG-PDLLA showed slow release and was easily engulfed by MM cells despite a result of the antitumor assay comparable to that of free melphalan in vitro.The in vivo results showed that MEL/MPEG-PDLLA could significantly alleviate tumor burden and prolong survival time without increasing the toxicity to vital organs.In addition,MEL/MPEG-PDLLA could significantly reduce the damage to the intestinal mucosa caused by melphalan.In conclusion,MEL/MPEG-PDLLA shows improved antitumor activity and has the potential to alleviate pains of MM patients undergoing ASCT.
基金supported by National Natural Science Foundation of China(No.82073830)Chongqing Natural Science Foundation(No.CSTB2022NSCQ-MSX1328).
文摘Colorectal cancer(CRC)is a common digestive tract tumor worldwide.Specific microorganisms,including Fusobacterium nucleatum(F.nucleatum)and Escherichia coli(E.coli),are abundant in colonic mucosa and can promote the cancer progression and malignancy.Therefore,a therapeutic strategy is proposed to deliver effective drugs to colorectum for both anticancer and antibacteria.Here we used thin-film dispersionmethod to encapsulate hemiprotonic phenanthroline-phenanthroline^(+)(ph-ph^(+))into nanomicelle.The results showed that the drug-loading nanomicelle had good dispersion,and the particle size was about 28 nm.In vitro assay indicated that the nanomicelle was active against CRC-related obligate and facultative anaerobes.In human CRC cells,the nanomicelle could effectively inhibit cell proliferation and induce apoptosis.In vivo distribution showed that the nanomicelle could release ph-ph^(+) mainly in the colorectum.In CRC model mice,the nanomicelle significantly reduced tumor number and volume,and decreased the bacteria load and colorectal inflammation.Together,the study identifies that the ph-ph^(+) nanomicelle has the potential to apply in treating CRC,and also suggests that anticancer combined with antimicrobial therapy would be a feasible way for CRC therapy.
基金the National Natural Science Foundation of China(No.81803466)the Key Areas Research and Development Program of Guangdong Province(No.2019B020204002)the Natural Science Foundation of Guangdong Province(No.2021A1515012525).
文摘Nanomedicine with high specificity has been a promising tool for cancer diagnosis and therapy.However,the successful application of nanoparticle-based superficial cancer therapy is severely hindered by restricted deep tumor tissue accumulation and penetration.Herein,a self-assembly nanomicelle dissolving microneedle(DMN)patch according to the“nano in micro”strategy was conducted to co-deliver a first-line chemotherapeutic agent paclitaxel(PTX),and a photosensitizer IR780(PTX/IR780-NMs@DMNs)for chemo-photothermal synergetic melanoma therapy.Upon direct insertion into the tumor site,DMNs created a regular and multipoint three-dimensional drug depot to maximize the tumor accumulation.Accompanied by the DMN dissolution,the composition of the needle matrixes self-assembled into nanomicelles,which could efficiently penetrate deep tumor tissue.Upon laser irradiation,the nanomicelles could not only ablate tumor cells directly by photothermal conversion but also trigger PTX release to induce tumor cell apoptosis.In vivo results showed that compared with intravenous injection,IR780 delivered by PTX/IR780-NMs@DMNs was almost completely accumulated at the tumor site.The antitumor results revealed that the PTX/IR780-NMs@DMNs could effectively eliminate tumors with an 88%curable rate without any damage to normal tissues.This work provides a versatile and generalizable framework for designing self-assembly DMN-mediated combination therapy to fight against superficial cancer.
基金Supported by Special Fund for Basic Scientific Research Business in Central Universities(2019NYB31)Scientific Research Funded Project of Southwest Minzu University(2023KYZZ06N).
文摘[Objectives]To prepare plumbagin nanomicelle(PLB-N)in-situ gel,and optimize the formulation and process.[Methods]PLB-N was prepared by self-assembly method,and the optimal formulation of PLB-N in-situ gel was determined by orthogonal experiment design and single factor method.[Results]The optimal preparation process for PLB-N was a drug to lipid ratio of 1:3,a Tween 80 content of 5%,an ethanol content of 7.5%of the hydration medium,a magnetic stirring speed of 2200 rpm,a stirring time of 30 min,and an ultrasound time of 10 min.The optimal formulation of PLB-N in-situ gel was 22%of poloxamer 407,6%of poloxamer 188,and 1:1 of PLB-N to water.The encapsulation efficiency of PLB-N prepared with the optimal formula was(95.8%±0.4%),and the average particle size was(75.19±1.14)nm,and the Zeta potential was(-20.73±1.19)mv.[Conclusions]PLB-N in-situ gel had stable and reliable preparation process,uniform content,and broad application prospects.
基金the Science and Technology Development Project of Shandong Province(No.2012GNC11307)the People's Livelihood Science and Technology Project of Qingdao(NO.14232nsh)
文摘Amphiphilic CS-SA polymers were prepared using the SA modified by small molecule water-soluble chitosan, and CS-SA nanomicelles and FF/CS-SA nanomicelles were prepared by using CSSA polymers as the material with dialysis-ultrasound method. CS-SA polymers, CS-SA nanomicelles, and FF/CS-SA nanomicelles were characterized by FT-IR, TGA, and SEM. Results showed that the SA was grafted to the amino of CS by amide bond. CS-SA nanomicelles and FF/CS-SA nanomicelles were spherical, smooth without fold. The influence of different molar ratio of FF to CS-SA polymers on the encapsulation efficiency and drug-loading rate determined the best molar ratio that was 1：1.09. In vitro release experiments, drug release performance study found that hydrophobic drug releasing from FF/CS-SA nanomicelles presented sustainedrelease. In vitro bacteriostasis experiments, when the concentration was higher than 4.98 mg/mL, FF/CSSA nanomicelles had antibacterial action and a positive correlation with concentration. The results revealed that amphiphilic chitosan derivative nanomicelles were carriers with broad prospects, increasing solubility of hydrophobic drugs and presenting sustained release for hydrophobic drugs, which provided a new research idea for drug delivery and targeted drug delivery of hydrohobic drugs.
文摘All-in-one treatments represent a paradigm shift in future medicine.For example,inflammatory bowel disease(IBD)is mainly diagnosed by endoscopy,which could be applied for not only on-site monitoring but also the intestinal lesion-targeted spray of injectable hydrogels.Furthermore,molecular conjugation to the hydrogels would program both lesion-specific adhesion and drug-free therapy.This study validated this concept of all-in-one treatment by first utilizing a well-known injectable hydrogel that underwent efficient solution-to-gel transition and nanomicelle formation as a translatable component.These properties enabled spraying of the hydrogel onto the intestinal walls during endoscopy.Next,peptide conjugation to the hydrogel guided endoscopic monitoring of IBD progress upon adhesive gelation with subsequent moisturization of inflammatory lesions,specifically by nanomicelles.The peptide was designed to mimic the major component that mediates intestinal interaction with Bacillus subtilis flagellin during IBD initiation.Hence,the peptide-guided efficient adhesion of the hydrogel nanomicelles onto Toll-like receptor 5(TLR5)as the main target of flagellin binding and Notch-1.The peptide binding potently suppressed inflammatory signaling without drug loading,where TLR5 and Notch-1 operated collaboratively through downstream actions of tumor necrosis factor-alpha.The results were produced using a human colorectal cell line,clinical IBD patient cells,gut-on-a-chip,a mouse IBD model,and pig experiments to validate the translational utility.
